Neolithisches Erdwerk oder Gelifluktionsloben? Archäologische und geowissenschaftliche Forschungen an einem geomagnetischen Befund aus Holzhausen, Ldkr. Oldenburg

Near Holzhausen in the District of Oldenburg, geomagnetic anomalies were detected by geomagnetic surveys. In view of the size and the concentric shape that emerged from the anomalies, the resulting structure was interpreted as an enclosure. To confirm this assumption, an archaeological excavation was carried out in 2010 and 2011. Due to the fact that the anomalies and the structure could not be satisfactorily explained by this, additional pedological and geological investigations were conducted. The result that the anomalies were generated by geological structures shows that the interpretation of geomagnetic measurements – in spite of good analogies – is limited without further field investigations

Ice Algae-Produced Carbon Is Critical for Overwintering of Antarctic Krill Euphausia superba

Antarctic krill Euphausia superba (“krill”) constitute a fundamental food source for Antarctic seabirds and mammals, and a globally important fisheries resource. The future resilience of krill to climate change depends critically on the winter survival of young krill. To survive periods of extremely low production by pelagic algae during winter, krill are assumed to rely partly on carbon produced by ice algae. The true dependency on ice algae-produced carbon, however, is so far unquantified. This confounds predictions on the future resilience of krill stocks to sea ice decline. Fatty acid (FA) analysis, bulk stable isotope analysis (BSIA), and compound-specific stable isotope analysis (CSIA) of diatom- and dinoflagellate-associated marker FAs were applied to quantify the dependency of overwintering larval, juvenile, and adult krill on ice algae-produced carbon (αIce) during winter 2013 in the Weddell-Scotia Confluence Zone. Our results demonstrate that the majority of the carbon uptake of the overwintering larval and juvenile krill originated from ice algae (up to 88% of the carbon budget), and that the dependency on ice algal carbon decreased with ontogeny, reaching <56% of the carbon budget in adults. Spatio-temporal variability in the utilization of ice algal carbon was more pronounced in larvae and juvenile krill than in adults. Differences between αIce estimates derived from short- vs. long-term FA-specific isotopic compositions suggested that ice algae-produced carbon gained importance as the winter progressed, and might become critical at the late winter-spring transition, before the phytoplankton bloom commences. Where the sea ice season shortens, reduced availability of ice algae might possibly not be compensated by surplus phytoplankton production during wintertime. Hence, sea ice decline could seriously endanger the winter survival of recruits, and subsequently overall biomass of krill

ADP-heptose enables Helicobacter pylori to exploit macrophages as a survival niche by suppressing antigen-presenting HLA-II expression

The persistence of Helicobacter pylori in the human gastric mucosa implies that the immune response fails to clear the infection. We found that H. pylori compromises the antigen presentation ability of macrophages, because of the decline of the presenting molecules HLA-II. Here, we reveal that the main bacterial factor responsible for this effect is ADP-heptose, an intermediate metabolite in the biosynthetic pathway of lipopolysaccharide (LPS) that elicits a pro-inflammatory response in gastric epithelial cells. In macrophages, it upregulates the expression of miR146b which, in turn, would downmodulate CIITA, the master regulator for HLA-II genes. Hence, H. pylori, utilizing ADP-heptose, exploits a specific arm of macrophage response to establish its survival niche in the face of the immune defense elicited in the gastric mucosa

Case Report: Simultaneously Induced Neutropenia and Hemolysis After a Single Metamizole Dose

Background and objective Metamizole is a non-opioid ampyrone sulfonate compound with potent analgesic, antipyretic, and spasmolytic effects. Agranulocytosis is a rare life-threatening complication of metamizole. Case Here, we present the case of a 62-year-old patient who developed agranulocytosis as well as hemolysis after a single administration of metamizole. Conclusion This case illustrates the inherent allergic potential of metamizole and its effects on different hematopoietic cell types

Twin-lattice atom interferometry

Inertial sensors based on cold atoms have great potential for navigation, geodesy, or fundamental physics. Similar to the Sagnac effect, their sensitivity increases with the space-time area enclosed by the interferometer. Here, we introduce twin-lattice atom interferometry exploiting Bose-Einstein condensates. Our method provides symmetric momentum transfer and large areas in palm-sized sensor heads with a performance similar to present meter-scale Sagnac devices

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

BACKGROUND: Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients. MATERIAL AND METHODS: Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months. RESULTS: Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6–8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion. CONCLUSIONS: Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs

Fusion of Bacterial Flagellin to a Dendritic Cell-Targeting αCD40 Antibody Construct Coupled With Viral or Leukemia-Specific Antigens Enhances Dendritic Cell Maturation and Activates Peptide-Responsive T Cells

Conventional dendritic cell (DC) vaccine strategies, in which DCs are loaded with antigens ex vivo, suffer biological issues such as impaired DC migration capacity and laborious GMP production procedures. In a promising alternative, antigens are targeted to DC-associated endocytic receptors in vivo with antibody–antigen conjugates co-administered with toll-like receptor (TLR) agonists as adjuvants. To combine the potential advantages of in vivo targeting of DCs with those of conjugated TLR agonists, we generated a multifunctional antibody construct integrating the DC-specific delivery of viral- or tumor-associated antigens and DC activation by TLR ligation in one molecule. We validated its functionality in vitro and determined if TLR ligation might improve the efficacy of such a molecule. In proof-of-principle studies, an αCD40 antibody containing a CMV pp65-derived peptide as an antigen domain (αCD40CMV) was genetically fused to the TLR5-binding D0/D1 domain of bacterial flagellin (αCD40.FlgCMV). The analysis of surface maturation markers on immature DCs revealed that fusion of flagellin to αCD40CMV highly increased DC maturation (3.4-fold elevation of CD80 expression compared to αCD40CMV alone) by specifically interacting with TLR5. Immature DCs loaded with αCD40.FlgCMV induced significantly higher CMVNLV-specific T cell activation and proliferation compared to αCD40CMV in co-culture experiments with allogeneic and autologous T cells (1.8-fold increase in % IFN-γ/TNF-α+ CD8+ T cells and 3.9-fold increase in % CMVNLV-specific dextramer+ CD8+ T cells). More importantly, we confirmed the beneficial effects of flagellin-dependent DC stimulation using a tumor-specific neoantigen as the antigen domain. Specifically, the acute myeloid leukemia (AML)-specific mutated NPM1 (mNPM1)-derived neoantigen CLAVEEVSL was delivered to DCs in the form of αCD40mNPM1 and αCD40.FlgmNPM1 antibody constructs, making this study the first to investigate mNPM1 in a DC vaccination context. Again, αCD40.FlgmNPM1-loaded DCs more potently activated allogeneic mNPM1CLA-specific T cells compared to αCD40mNPM1. These in vitro results confirmed the functionality of our multifunctional antibody construct and demonstrated that TLR5 ligation improved the efficacy of the molecule. Future mouse studies are required to examine the T cell-activating potential of αCD40.FlgmNPM1 after targeting of dendritic cells in vivo using AML xenograft models

High-resolution Visualization of Intestinal Microcirculation using Ultra-microangiography in Patients with Inflammatory Bowel Disease: A Pilot Study

Background & Aims: Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA. Methods: We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control. Results: Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA. Conclusions: To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD